Business Overview and History
Edgewise Therapeutics, Inc. (NASDAQ: EWTX) is a leading biopharmaceutical company dedicated to developing innovative treatments for severe muscle diseases. With a strong focus on precision medicine and a deep understanding of muscle biology, Edgewise has built a robust pipeline of product candidates targeting various muscle-related disorders, including muscular dystrophies and cardiac conditions.
Edgewise Therapeutics was incorporated as a Delaware corporation in May 2017 and is headquartered in Boulder, Colorado. The company was co-founded by Chief Scientific Officer Alan Russell, Ph.D., Peter Thompson, M.D., who is currently a Partner at OrbiMed, and Badreddin Edris, Ph.D., who is currently the Chief Operating Officer at SpringWorks Therapeutics, Inc. through funding provided by OrbiMed.
From its inception, Edgewise has been focused on the discovery, development and commercialization of innovative treatments for severe muscle diseases for which there is significant unmet medical need. The company has built a proprietary, muscle-focused drug discovery platform that utilizes custom-built high throughput and translatable systems to identify small molecule precision medicines regulating key proteins in muscle tissue. This platform has generated several programs to address a variety of muscle diseases.
In 2017, Edgewise raised $160.7 million from leading institutional investors which include OrbiMed, Novo Holdings AS, U.S. Venture Partners (USVP), Deerfield Management, Viking Global Investors, New Leaf Ventures, Janus Henderson Investors, RA Capital Management, Cormorant Asset Management, Logos Capital, Wellington Management, CureDuchenne Ventures and an undisclosed institutional investor. The company then raised an additional $186.1 million in net proceeds from its initial public offering in March 2021, $129.2 million in net proceeds from a follow-on public offering in September 2022, $59.4 million in net proceeds through an at-the-market offering program, and $231.9 million in net proceeds from an underwritten registered direct offering in January 2024.
Edgewise's lead product candidates, sevasemten and EDG-7500, are advancing through clinical development. Sevasemten is an orally administered small molecule designed to prevent contraction-induced muscle damage in dystrophinopathies, including Duchenne muscular dystrophy (Duchenne) and Becker muscular dystrophy (Becker). EDG-7500, on the other hand, is a novel, oral, selective cardiac sarcomere modulator being evaluated for the treatment of hypertrophic cardiomyopathy (HCM).
Sevasemten, Edgewise's most advanced program, has demonstrated promising results in preclinical studies and early-stage clinical trials. The company is currently conducting multiple Phase 2 clinical trials, including the CANYON trial in individuals with Becker and the LYNX and FOX trials in patients with Duchenne. The CANYON trial recently met its primary endpoint, showing a significant reduction in circulating levels of creatine kinase (CK), a biomarker associated with skeletal muscle damage, in the sevasemten-treated group.
In addition to its lead programs, Edgewise is advancing its EDG-3.00 cardiometabolic discovery program, exploring novel targets and mechanisms to address a variety of muscle-related disorders.
Financial Highlights
As of December 31, 2024, Edgewise reported cash, cash equivalents, and marketable securities of $470.2 million, providing the company with a strong financial position to support its ongoing research and development efforts.
For the year ended December 31, 2024, Edgewise reported no revenue and a net loss of $133.8 million. The company's research and development expenses amounted to $126.9 million, reflecting its focus on advancing its clinical-stage programs and preclinical research. General and administrative expenses were $31.9 million, primarily related to personnel costs and professional fees.
In the most recent quarter (Q4 2024), Edgewise reported no revenue and a net loss of $39.7 million. As a clinical-stage biopharmaceutical company, Edgewise has not yet generated product revenue, which is typical for companies at this stage of development.
The biopharmaceutical industry focused on rare neuromuscular and cardiac diseases has seen a compound annual growth rate (CAGR) of approximately 10-15% in recent years. This growth is driven by increased investment and drug development in areas with high unmet medical need, aligning well with Edgewise's focus on innovative treatments for severe muscle diseases.
Liquidity
Edgewise's balance sheet remains healthy, with a current ratio of 19.9 and a quick ratio of 19.9 as of December 31, 2024, indicating a robust liquidity position. The company's total debt stood at $4.7 million, primarily comprising lease obligations, resulting in a debt-to-equity ratio of 0.01. Total equity was reported at $459.2 million.
The company's strong liquidity is further evidenced by its cash, cash equivalents, and short-term investments of $470.2 million as of December 31, 2024. This substantial cash position provides Edgewise with the financial flexibility to fund its planned operating expenses and capital expenditure requirements for at least the next 12 months.
Operational Highlights and Upcoming Milestones
In 2024, Edgewise made significant progress in advancing its clinical pipeline and strengthening its leadership team. Key operational highlights include:
1. Completion of enrollment for the GRAND CANYON pivotal cohort of the CANYON trial evaluating sevasemten in Becker, including over-enrolling beyond the target 120 adult participants. 2. Announcement of positive topline results from the CANYON trial, which met the primary endpoint of reduction in circulating levels of CK and showed a trend towards stabilization of the North Star Ambulatory Assessment (NSAA) in sevasemten-treated patients. 3. Initiation of the LYNX and FOX Phase 2 trials evaluating sevasemten in children and adolescents with Duchenne. 4. Completion of the Phase 1 trial of EDG-7500 in healthy subjects and the Part A single-dose arm of the Phase 2 CIRRUS-HCM trial in patients with obstructive HCM, with positive topline data. 5. Strengthening of the leadership team with the appointment of Robert Blaustein, M.D., Ph.D., as Chief Development Officer and the promotion of Behrad Derakhshan, Ph.D., to Chief Operating Officer.
Looking ahead, Edgewise has several key milestones planned for 2025:
- Reporting data from the Phase 2 CIRRUS-HCM trial of EDG-7500 in the first quarter of 2025. - Reporting data from the Phase 2 LYNX and FOX trials of sevasemten in Duchenne in the first half of 2025. - Potential regulatory submissions for sevasemten in Becker, based on the positive CANYON trial results.
Product Pipeline and Clinical Development
Muscular Dystrophy Program: Sevasemten Sevasemten is an orally administered, allosteric, selective, fast myofiber type II myosin inhibitor designed to address the root cause of dystrophinopathies, including Duchenne and Becker muscular dystrophies. The drug is currently being studied in multiple Phase 2 clinical trials.
The CANYON Phase 2 trial in individuals with Becker met its primary endpoint, demonstrating a significant change from baseline in circulating levels of creatine kinase (CK). On the key secondary endpoint, sevasemten-treated patients showed stabilization of the North Star Ambulatory Assessment (NSAA) score, with a trend towards improvement at 12 months compared to placebo. Based on these positive results, Edgewise expanded CANYON to include a potentially registrational cohort called GRAND CANYON, which completed enrollment in February 2025.
In Duchenne, Edgewise is advancing two Phase 2 studies - LYNX and FOX. LYNX is assessing the safety, pharmacokinetics, and biomarkers of muscle damage in individuals with Duchenne, while FOX is evaluating sevasemten in children and adolescents with Duchenne who have been previously treated with gene therapy.
The FDA has granted sevasemten Fast Track designation for the treatment of Duchenne and Orphan Drug Designation for the treatment of both Duchenne and Becker.
Cardiovascular Program: EDG-7500 EDG-7500 is a novel, oral, selective cardiac sarcomere modulator being developed for the treatment of hypertrophic cardiomyopathy (HCM). It is currently being evaluated in the CIRRUS-HCM Phase 2 trial, a four-part, multi-center, open-label study in patients with both obstructive and non-obstructive HCM.
In the single-dose Part A of the CIRRUS-HCM trial, EDG-7500 demonstrated robust reductions in left ventricular outflow tract (LVOT) gradient without meaningful changes in left ventricular ejection fraction. EDG-7500 also led to a 64% mean reduction in NT-proBNP, a key biomarker of heart failure, in the 200 mg cohort.
Edgewise is currently amending Part D of the CIRRUS-HCM trial as it plans for a Phase 3 study of EDG-7500 in 2026. The company expects to report initial data from Parts B and C of CIRRUS-HCM in the first quarter of 2025, and from the open-label extension Part D in the second half of 2025.
Risks and Challenges
As a clinical-stage biopharmaceutical company, Edgewise faces several risks and challenges common to the industry, including:
1. Clinical development risks: The success of Edgewise's product candidates is dependent on the outcome of ongoing and future clinical trials, which can be unpredictable and subject to delays or failures. 2. Regulatory approval hurdles: Obtaining regulatory approvals from the FDA, EMA, and other authorities for Edgewise's product candidates is a complex and time-consuming process, with no guarantee of success. 3. Competition and market acceptance: Edgewise's product candidates may face competition from existing or emerging therapies, and the company's ability to achieve market acceptance will be crucial for commercial success. 4. Reliance on third-party manufacturers and suppliers: Edgewise's dependence on third-party partners for the manufacture and supply of its product candidates introduces potential risks related to quality, availability, and cost. 5. Intellectual property protection: Maintaining and defending Edgewise's intellectual property rights is essential to preserving the company's competitive advantage and the value of its pipeline.
Conclusion
Edgewise Therapeutics is a promising biopharmaceutical company at the forefront of developing innovative therapies for severe muscle diseases. With a robust pipeline, including the advanced-stage sevasemten and EDG-7500 programs, the company is well-positioned to address significant unmet medical needs in muscular dystrophies and cardiac conditions.
Edgewise's strong financial position, with over $470 million in cash, cash equivalents, and marketable securities, provides the necessary resources to support its ongoing research and development efforts. The company's recent operational achievements, including the positive CANYON trial results for sevasemten, demonstrate its ability to execute on its strategic priorities.
As Edgewise continues to advance its pipeline and navigate the regulatory landscape, the company's success will be closely watched by investors and the broader muscle disease community. With its deep understanding of muscle biology and commitment to precision medicine, Edgewise Therapeutics remains a compelling investment opportunity in the biopharmaceutical sector.